Chernoff Neil, Hill Donna, Lang Johnsie, Schmid Judith, Farthing Amy, Huang Hwa
Center for Public Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Oak Ridge Institute for Science and Education, Oak Ridge, TN 37831, USA.
Toxins (Basel). 2021 Jan 24;13(2):86. doi: 10.3390/toxins13020086.
Microcystins are common freshwater cyanobacterial toxins that affect liver function. The toxicities of five microcystin congeners (microcystin-LA (MCLA), MCLR, MCLY, MCRR, and MCYR) commonly observed in harmful algal blooms (HABs) were evaluated in BALB/c mice after a single oral administration of doses ranging from those that were no observed adverse effect levels (NOAELs) to lowest observed adverse effect levels (LOAELs). Animals were monitored for changes in behavior and appearance, and euthanized 24 h after dosing. Test endpoints included clinical changes, necropsy observations, and serum indicators of hepatic toxicity and general homeostasis. Doses were 0.5-7 mg/kg MCLA, 0.5-11 mg/kg MCLR, 1-7 mg/kg MCLY, 7-22 mg/kg MCRR, and 3-11 mg/kg MCYR. MCLA at 3 mg/kg elevated liver/body weight ratio and liver score, ALT, AST, and GLDH, indicating hepatic toxicity, reduced serum glucose and highly elevated total serum bilirubin. MCLR and MCLY induced similar effects with LOAELs of 5 mg/kg, although a greater extent and severity of effects were observed in MCLR animals. MCRR exposure at 22 mg/kg was associated with reduced serum glucose. MCYR induced scattered liver effects at 7 mg/kg and reduced serum glucose levels at 5 mg/kg. The results indicate significant differences in congener-induced toxicity after microcystin exposure.
微囊藻毒素是常见的淡水蓝藻毒素，会影响肝功能。在BALB/c小鼠单次口服给予从未观察到不良反应水平（NOAELs）到最低观察到不良反应水平（LOAELs）范围内的剂量后，评估了有害藻华（HABs）中常见的五种微囊藻毒素同系物（微囊藻毒素-LA（MCLA）、MCLR、MCLY、MCRR和MCYR）的毒性。监测动物的行为和外观变化，并在给药后24小时实施安乐死。测试终点包括临床变化、尸检观察以及肝毒性和一般内环境稳定的血清指标。剂量分别为0.5 - 7 mg/kg MCLA、0.5 - 11 mg/kg MCLR、1 - 7 mg/kg MCLY、7 - 22 mg/kg MCRR和3 - 11 mg/kg MCYR。3 mg/kg的MCLA使肝/体重比和肝脏评分、谷丙转氨酶（ALT）、谷草转氨酶（AST）和谷氨酸脱氢酶（GLDH）升高，表明有肝毒性，血清葡萄糖降低且总血清胆红素大幅升高。MCLR和MCLY诱导了类似的效应，LOAEL为5 mg/kg，不过在MCLR组动物中观察到的效应程度和严重程度更大。22 mg/kg的MCRR暴露与血清葡萄糖降低有关。7 mg/kg的MCYR诱导了散在的肝脏效应，5 mg/kg时血清葡萄糖水平降低。结果表明微囊藻毒素暴露后同系物诱导的毒性存在显著差异。
